Biomedical subjects

Koichi Inoue

Publications and source records attributed to Koichi Inoue.

At least 19 recordsLinked to original sources

PubMed2026

ALID score for treatment-effect heterogeneity of adjunctive low-voltage area ablation in persistent atrial fibrillation: A post hoc analysis of SUPPRESS-AF.

BACKGROUND: In persistent atrial fibrillation (AF), the incremental benefit of adjunctive low-voltage area (LVA) ablation beyond pulmonary vein isolation (PVI) remains inconsistent. OBJECTIVE: To examine whether a simple clinical score characterizes treatment-effect heterogeneity of adjunctive LVA ablation among patients with mapped LVA > 5 cm2 and to perform an exploratory supportive analysis in an independent randomized cohort. METHODS: In this post-hoc analysis of SUPPRESS-AF, which included patients with persistent AF and mapped LVA > 5 cm2 after PVI, four variables-age ≥ 75 years, left atrial diameter > 44 mm, estimated glomerular filtration rate < 60 mL/min/1.73 m2, and absence of diabetes-were combined into the ALID score (0-4). Patients were stratified into low (0-1), intermediate (2), and high (3-4) score groups. Because EARNEST-PVI did not use LVA-guided ablation or select patients based on mapped LVA, it was analyzed as an exploratory supportive cohort rather than as an external validation cohort. RESULTS: In SUPPRESS-AF (n = 336), a significant treatment-by-score interaction was observed (P < 0.001). Adjunctive LVA ablation was associated with increased recurrence in the low-score stratum (HR 3.92; 95% CI 1.50-10.20) and reduced recurrence in the high-score stratum (HR 0.48; 95% CI 0.26-0.86). In EARNEST-PVI (n = 494), a qualitatively similar interaction pattern was observed for additional ablation beyond PVI (interaction P = 0.029), although the ablation strategy differed from LVA-guided ablation. CONCLUSIONS: Among patients with persistent AF and mapped LVA >5 cm2, the ALID score identified heterogeneity in response to adjunctive LVA ablation. These hypothesis-generating findings require prospective validation before clinical implementation.

Humans↗

PubMed2007

Detection and quantification of embolic particles during percutaneous coronary intervention to stable plaque: it correlates to coronary flow dynamics and myocardial damage.

OBJECTIVES: We detected embolic particles liberated from plaque during percutaneous coronary intervention (PCI) as high-intensity transient signals (HITS) with a Doppler guidewire and studied their impact on coronary flow dynamics and the myocardium in patients with stable angina pectoris. BACKGROUND: These embolic particles during PCI may cause myocardial injury. However, this was difficult to confirm because it was impossible to detect embolic particles. METHODS: We performed balloon angioplasty followed by stenting in 31 patients while monitoring coronary flow velocity. After PCI, we measured average peak velocity at baseline and after infusion of adenosine 5'-triphosphate to calculate coronary flow velocity reserve (CFVR) and coronary resistance index (CRI). In patients with PCI to the left coronary artery (n = 21), we calculated relative CFVR as the ratio of CFVR in the target vessel to that in the reference vessel. We measured cardiac troponin T (cTnT) the day after PCI. RESULTS: HITS were detected in 27 (87%) of 31 patients and the majority were observed after stenting. The total number of HITS was correlated with CRI (r = 0.36, P = 0.049) or relative CFVR (r = 0.65, P = 0.0036) but not with CFVR (r = 0.048, P = 0.82). Thirteen patients showed elevated cTnT (range, 0.05-0.31 ng/ml) and the total number of HITS was greater in those with elevated cTnT than in those without elevated cTnT (24 +/- 9 vs. 10 +/- 7, P = 0.0007). CONCLUSIONS: Embolic particles are frequently observed during PCI to stable plaque and the majority are liberated after stenting. There appears to be a quantitative relationship between amounts of HITS and coronary microvessel dysfunction and minor myocardial injury.

Aged↗

PubMed2006

Marshall vein as arrhythmogenic source in patients with atrial fibrillation: correlation between its anatomy and electrophysiological findings.

BACKGROUND: Atrial fibrillation (AF) may originate from catecholamine-sensitive vein of Marshall (VOM) or its ligament in addition to pulmonary veins (PVs). The anatomy of VOM and its relation to arrhythmogenic foci in the left atrium are unknown. We studied the anatomy of VOM and its relation to foci in patients with AF. METHODS: The study population consisted of 100 patients with AF (mean age, 62 years; chronic AF, n = 15). AF sources were determined at baseline and after isoproterenol administration without sedation. VOM was identified by balloon-occluded coronary sinus (CS) angiography. We determined its anatomy in relation to left PVs. RESULTS: VOM was visualized in 73 patients (73%). Ninety-seven patients had 269 arrhythmogenic foci (PV, n = 77; non-PV, n = 48). Non-PV foci included left atrial posterior wall (24, 9%), left lateral area (12, 4.5%), roof (6, 2.2%), superior vena cava (28, 10.4%), crista terminalis (8, 3.0%), CS (10, 3.7%), and others (10, 3.7%). The incidence of PV foci in the left superior PV (LSPV) was significantly higher in patients with well-developed VOM than in those without (66% vs 42%, P < 0.05). Twenty-eight patients had 30 non-PV foci around the LSPV ostium. We successfully ablated the non-PV foci at the distal end of VOM in 11 patients. The ends of the VOM branches were good markers to search for non-PV foci. Seven of 11 (64%) patients with successful ablation of non-PV foci were free from arrhythmia, whereas only 6 of 17 (35%) were free from arrhythmia in those with residual non-PV foci. CONCLUSIONS: To determine VOM anatomy is important to identify non-PV foci around the ends of VOM.

Atrial Fibrillation↗

PubMed2006

Comparison of orifice area by transthoracic three-dimensional Doppler echocardiography versus proximal isovelocity surface area (PISA) method for assessment of mitral regurgitation.

Effective regurgitant orifice area is a useful index of the severity of mitral regurgitation (MR). The calculation of regurgitant orifice area using the proximal isovelocity surface area (PISA) method has some technical limitations. Three-dimensional reconstruction of the MR jet was performed using the Live 3D system on a Sonos 7500 to measure regurgitant orifice area directly in 109 cases of MR. Regurgitant orifice area was also measured by quantitative 2-dimensional echocardiography and by the PISA method. To analyze the shape of the regurgitant orifice, the ratio of the long axis to the short axis of the orifice (the L/S ratio) was calculated. Regurgitant orifice area on 3-dimensional echocardiography showed an almost identical correlation with that obtained by quantitative echocardiography (r = 0.91, p <0.0001, slope = 0.97) regardless of the L/S ratio. It was also significantly correlated with orifice area obtained using the PISA method (r = 0.93, p <0.0001). However, orifice area on 3-dimensional echocardiography was significantly larger than that obtained using the PISA method in the whole study group and in the 62 cases of MR with L/S ratios >1.5, whereas the correlation was almost identical in cases of MR with L/S ratios < or =1.5. Orifice area obtained using the PISA method also underestimated that obtained by quantitative echocardiography in cases of MR with L/S ratios >1.5. Three-dimensional echocardiography provided robust values independent of the eccentricity of the MR jet or of cardiac rhythm. In conclusion, the direct measurement of the regurgitant orifice area of MR with 3-dimensional Doppler echocardiography could be a promising method to overcome the limitations of the PISA method, especially in cases of MR with elliptic orifice shapes.

Aged↗

PubMed2006

Usefulness of high-resolution real-time three-dimensional echocardiography to visualize the left ventricular endocardial surface in myocardial infarction.

High-resolution real-time 3-dimensional echocardiography (RT3DE) allows observation of the left ventricular endocardial surface in vivo. This study was performed to characterize the endocardial surface structure and its contractile function in the myocardial infarction (MI) zone in relation to the healing stage. RT3DE was performed in 90 subjects: 10 normal subjects, 50 patients with Q-wave MI 2 weeks after onset (acute MI), and 30 patients >2 months after onset (healed MI). Recordings of the left ventricular endocardial surface allowed observation of the endocardial structure in 76 patients (84%) from the apical window. The endocardial surface of normal myocardium has rough muscle folds that shrink during systole, implying endocardial contraction. In acute MI, the endocardial surface had lost systolic contraction, but appeared as normal surface structure and showed normal acoustic intensity. The endocardial surface of healed MI showed loss of systolic contraction, disappearance of folds (smooth surface), and high acoustic intensity. The frequencies of smooth surface and highest acoustic intensity were significantly higher in healed MI than acute MI (72% vs 32%, 68% vs 37%, p <0.05, respectively). Loss of systolic endocardial contraction was a common finding of Q-wave MI irrespective of the healing stage, and we could roughly estimate the size of the MI from the spatial extent of the noncontractile zone with reasonable reproducibility (r = 0.90, p <0.001). In conclusion, RT3DE is a new modality that allows observation of the structure and contraction of the endocardial surface of the left ventricular wall. We can make rough estimation of the size of the MI and its healing stage from endocardial observation with RT3DE.

Adult↗

PubMed2006

Chronic pre-treatment of statins is associated with the reduction of the no-reflow phenomenon in the patients with reperfused acute myocardial infarction.

AIMS: Early statin treatment has beneficial effects on prognosis after acute coronary syndrome. The no-reflow phenomenon determines the prognosis after acute myocardial infarction. We investigated the effects of statin treatment before admission on the development of the no-reflow after infarction. METHODS AND RESULTS: We performed intracoronary myocardial contrast echocardiography in 293 consecutive patients with acute myocardial infarction undergoing successful primary percutaneous coronary intervention. There were no significant differences in the incidence of the no-reflow between the patients with and without hypercholesterolaemia. The 33 patients receiving chronic statin treatment before admission had lower incidence of the no-reflow than those without it (9.1 and 34.6%, P=0.003). They also showed better wall motion, smaller left ventricular dimensions, and better ejection fraction at 4.9+/-2.2 months later. Multivariable logistic regression analysis revealed that statin pre-treatment was a significant predictor of the no-reflow along with anterior wall infarction, ejection fraction on admission, and additional ST-elevation after reperfusion, whereas total cholesterol was not. CONCLUSION: Chronic pre-treatment with statins could preserve the microvascular integrity after acute myocardial infarction independent of lipid lowering, leading to better functional recovery.

Adult↗

PubMed2006

Effect of reactive hyperemia after coronary recanalization on myocardial tissue reperfusion by thrombolysis in myocardial infarction flow grade in acute myocardial infarction.

Thrombolysis In Myocardial Infarction (TIMI) flow grade is widely used to evaluate myocardial tissue reperfusion in acute myocardial infarction (AMI), but the current grading system is incomplete. Therefore, we clarified the regulation of epicardial coronary flow velocity with the progression of microvascular dysfunction in AMI. We studied 36 patients with first anterior AMI. After intervention, we assessed TIMI flow grade and measured average peak velocity (APV) at baseline and after infusion of adenosine triphosphate (48 microg; baseline and hyperemic APVs, respectively) with a Doppler guidewire. We performed myocardial contrast echocardiography after 2 weeks to assess microvascular integrity (good reflow vs no reflow) and left ventriculography at admission and discharge (24 +/- 2 days) to measure regional wall motion (SD/chord). Patients were classified into 3 groups based on TIMI flow grade and microvascular integrity: TIMI grade 3 flow/good reflow (n = 16), TIMI grade 3 flow/no reflow (n = 12), and TIMI grade 2 flow (n = 8). Baseline APV was comparable in the patients with TIMI grade 3 flow but hyperemic APV was higher in patients with TIMI grade 3 flow/good reflow than in those with TIMI grade 3 flow/no reflow (hyperemic APV 59.3 +/- 25.8 vs 32.8 +/- 8.9 cm/s, p <0.01). All patients with TIMI grade 2 flow showed no reflow and the lowest values of baseline and hyperemic APVs. Regional wall motion at discharge was higher in patients with TIMI grade 3 flow/good reflow than in those with TIMI grade 3 flow/no reflow and TIMI grade 2 flow (-1.44 +/- 0.70, -2.69 +/- 0.31, and -2.88 +/- 0.48 SD/chord, respectively, p <0.01). In conclusion, compensatory reactive hyperemia preserves epicardial coronary flow velocity even in patients with microvascular damage, and with the progression of damage, this compensatory hyperemia can no longer preserve epicardial coronary flow velocity, and baseline APV is decreased in TIMI grade 2 flow.

Adult↗

PubMed2006

Liquid chromatography/tandem mass spectrometry characterization of oxidized amyloid beta peptides as potential biomarkers of Alzheimer's disease.

Alzheimer's disease is characterized by the deposition of senile plaques that consist primarily of amyloid beta peptides. There is substantial evidence that amyloid beta is oxidized in vivo, which has led to the suggestion that oxidative stress is an important mediator of Alzheimer's disease. Metal-catalyzed oxidation can mimic in vivo oxidation of amyloid beta because the metal ion binds to the amino acid residues at the site of oxidation, which then deliver reactive oxygen species to that site. Based on electrospray mass spectrometry, it has been suggested that metal-catalyzed oxidation occurs on histidines-13 and -14. Unfortunately, the amyloid beta peptides provide complex spectra, so it is difficult to definitively characterize the sites of oxidation. Trypsin digestion of both native and oxidized amyloid beta1-16 and amyloid beta1-40 resulted in the formation of tryptic peptides corresponding to amyloid beta6-16, which could be separated by liquid chromatography (LC). Sites of oxidation were then unequivocally characterized as histidine-13 and histidine-14 by LC/tandem mass spectrometric (MS/MS) analysis of the tryptic peptides. The ability to analyze the specific amyloid beta6-16 tryptic fragments derived from full-length amyloid beta peptides will make it possible to determine whether oxidation in vivo occurs at specific histidine residues and/or at other amino acid residues such as methionine-35. Using methodology based on LC/MS/MS it will also be possible to analyze the relative amounts of oxidized peptides and native peptide in cerebrospinal fluid from patients with Alzheimer's disease as biomarkers of oxidative stress.

Alzheimer Disease↗

PubMed2006

Quantitative analysis of amyloid beta peptides in cerebrospinal fluid of Alzheimer's disease patients by immunoaffinity purification and stable isotope dilution liquid chromatography/negative electrospray ionization tandem mass spectrometry.

The 40 and 42 amino-acid residue forms of amyloid beta (Abeta(1-40) and Abeta(1-42)) in cerebrospinal fluid (CSF) have been proposed as potential biomarkers of Alzheimer's disease (AD). Quantitative analyses of Abeta peptides in CSF have relied almost exclusively on the use of immunoassay-based assays such as the enzyme-linked immunosorbent assay (ELISA) procedure. However, due to the ability of the Abeta peptides to readily self-aggregate or bind to other proteins and glassware, such analyses are extremely challenging. Analyses are further complicated by the potential of the peptides to undergo post-translational modifications and the possibilities for cross-reaction in the ELISA assays with endogenous components of the CSF. An approach based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) has now been developed which overcomes these methodological issues. The key steps in implementing this new approach involved immunoaffinity purification coupled with the use of [15N]-labeled Abeta peptides as internal standards, a basic LC mobile phase, negative ion electrospray ionization, and a basic solvent for dissolving the peptides and washing the injection needle to prevent carryover of analytes during multiple injections on the LC/MS system. The validated method had limits of quantitation of 44 fmol/mL (200 pg/mL) for Abeta(1-42) and 92 fmol/mL (400 pg/mL) for Abeta(1-40). An excellent correlation was found between the LC/MS/MS assay and an ELISA assay for Abeta(1-42) in human CSF (r2 = 0.915), although less correlation was observed for Abeta(1-40) (r2 = 0.644). Mean CSF Abeta(1-42) concentrations for samples collected 2 weeks apart from a limited number of AD patients provided additional confidence in the reproducibility of the LC/MS/MS assay. Concentrations for duplicate samples from AD patients were slightly higher than most previously reported values (mean 1.06 +/- 0.25 ng/mL; n = 7). Abeta(1-40) concentrations in duplicate samples obtained from AD patients were also reproducible but were found to be slightly lower than most previously reported values (mean 6.36 +/- 3.07 ng/mL; n = 7). Consistent with literature reports, mean Abeta(1-42) concentrations were found to be lower in AD patients compared with the normal subjects (mean 1.49 +/- 0.59 ng/mL; n = 7), whereas there was no difference in Abeta(1-40) concentrations between AD patients and normal subjects (mean 5.88 +/- 3.03 ng/mL; n = 7). The accuracy and precision of the LC/MS assay mean that it will be a useful complement to existing ELISA assays for monitoring therapeutic interventions designed to modulate CSF Abeta(1-42) concentrations in individual AD patients. Moreover, the introduction of stable isotope labeled internal standards offers the potential to achieve a more rigorous account of the influence of methodological effects related to sample collection and processing.

Alzheimer Disease↗

PubMed2006

Era and RbfA have overlapping function in ribosome biogenesis in Escherichia coli.

A cold-shock protein, RbfA (ribosome-binding factor A), is essential for cell growth at low temperature. In an rbfA-deletion strain, 30S and 50S ribosomal subunits increase relative to 70S monosomes with concomitant accumulation of a precursor 16S rRNA (17S rRNA). Recently, we have reported that overexpression of Era, an essential GTP-binding protein, suppresses not only the cold-sensitive cell growth but also defective ribosome biogenesis in the rbfA-deletion strain. Here, in order to elucidate how RbfA and Era functionally overlap, we characterized a cold-sensitive Era mutant (a point mutation at the Glu-200 to Lys; E200K) which shows a similar phenotype as the rbfA-deletion strain; accumulation of free ribosome subunits and 17S rRNA. To examine the effect of E200K in the rbfA-deletion strain, we constructed an E200K-inducible expression system. Interestingly, unlike wild-type Era, overexpression of Era(E200K) protein in the rbfA-deletion strain severely inhibited cell growth even at permissive temperature with further concomitant reduction of 16S rRNA. Purified Era(E200K) protein binds to 30S ribosomal subunits in a nucleotide-dependent manner like wild-type Era and retains both GTPase and autophosphorylation activities. Furthermore, we isolated spontaneous revertants of the E200K mutant. These revertants partially suppressed the accumulation of 17S rRNA. All the spontaneous mutations were found to result in higher Era(E200K) expression. These results suggest that the Era(E200K) protein has an impaired function in ribosome biogenesis without losing its ribosome binding activity. The severe growth defect caused by E200K in the rbfA-deletion strain may be due to competition between intrinsic wild-type Era and overexpressed Era(E200K) for binding to 30S ribosomal subunits. We propose that Era and RbfA have an overlapping function that is essential for ribosome biogenesis, and that RbfA becomes dispensable only at high temperatures because Era can complement its function only at higher temperatures.

Escherichia coli↗

PubMed2006

Decreased serum free testosterone in workers exposed to high levels of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP): a cross-sectional study in China.

BACKGROUND: Observations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled increasing public concern regarding the potential for various chemicals to impair human fertility. OBJECTIVE: Our objective in this study was to assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol. METHODS: We examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) and compared them with samples from 63 male workers from a construction company, group matched for age and smoking status. RESULTS: Compared to the unexposed workers, the exposed workers had substantially and significantly elevated concentrations of mono-n-butyl phthalate (MBP; 644.3 vs. 129.6 microg/g creatinine, p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; 565.7 vs. 5.7 microg/g creatinine, p < 0.001). fT was significantly lower (8.4 vs. 9.7 microg/g creatinine, p = 0.019) in exposed workers than in unexposed workers. fT was negatively correlated to MBP (r = -0.25, p = 0.03) and MEHP (r = -0.19, p = 0.095) in the exposed worker group. Regression analyses revealed that fT decreases significantly with increasing total phthalate ester score (the sum of quartiles of MBP and MEHP; r = -0.26, p = 0.002). CONCLUSION: We observed a modest and significant reduction of serum fT in workers with higher levels of urinary MBP and MEHP compared with unexposed workers.

Adult↗

PubMed2006

Schedule-dependent interactions between pemetrexed and cisplatin in human carcinoma cell lines in vitro.

The combination of pemetrexed and cisplatin shows good clinical activity against mesothelioma and lung cancer. In order to study the potential cellular basis for this, and provide leads as to how to optimize the combination, we studied the schedule-dependent cytotoxic effects of pemetrexed and cisplatin against four human cancer cell lines in vitro. Tumor cells were incubated with pemetrexed and cisplatin for 24 h at various schedules. The combination effects after 5 days were analyzed by the isobologram method. Both simultaneous exposure to pemetrexed and cisplatin for 24 h and sequential exposure to cisplatin for 24 h followed by pemetrexed for 24 h produced antagonistic effects in human lung cancer A549, breast cancer MCF7, and ovarian cancer PA1 cells and additive effects in colon cancer WiDr cells. Pemetrexed for 24 h followed by cisplatin for 24 h produced synergistic effects in MCF7 cells, additive/synergistic effects in A549 and PA1 cells, and additive effects in WiDr cells. Cell cycle analysis of MCF7 and PA1 cells supported these findings. Our results suggest that the simultaneous clinical administration of pemetrexed and cisplatin may be suboptimal. The optimal schedule of pemetrexed in combination with cisplatin at the cellular level is the sequential administration of pemetrexed followed by cisplatin and this schedule is worthy of clinical investigations.

Carcinoma↗

PubMed2006

[Prevention of osteoporosis by foods and dietary supplements. What are foods for specified health uses (FOSHU)?].

Foods for specified health uses (FOSHU) are foods to which a "functional" ingredient has been added for a specific healthful effect. Approved by the Ministry of Health, Labour and Welfare, these foods have been designed to maintain and promote good health. Main guidelines for application, evaluation and labeling for FOSHU is following. (1)FOSHU should be evaluation in its effectiveness and safety scientifically by the Council of Pharmaceutical affairs and Food Hygiene and Food Safety Commission. (2)Functional labeling of FOSHU should be on science basis, but should not imply prevention, treatment and diagnosis of human disease.

Food, Organic↗

PubMed2005

Brain-type creatine kinase activates neuron-specific K+-Cl- co-transporter KCC2.

GABA, a major inhibitory neurotransmitter in the adult CNS, is excitatory at early developmental stages as a result of the elevated intracellular Cl- concentration ([Cl-]i). This functional switch is primarily attributable to the K+-Cl- co-transporter KCC2, the expression of which is developmentally regulated in neurons. Previously, we reported that KCC2 interacts with brain-type creatine kinase (CKB). To elucidate the functional significance of this interaction, HEK293 cells were transfected with KCC2 and glycine receptor alpha2 subunit, and gramicidin-perforated patch-clamp recordings were performed to measure the glycine reversal potential (Egly), giving an estimate of [Cl-]i. KCC2-expressing cells displayed the expected changes in Egly following alterations in the extracellular K+ concentration ([K+]o) or administration of an inhibitor of KCCs, suggesting that the KCC2 function was being properly assessed. When added into KCC2-expressing cells, dominant-negative CKB induced a depolarizing shift in Egly and reduced the hyperpolarizing shift in Egly seen in response to a lowering of [K+]o compared with wild-type CKB. Moreover, 2,4-dinitrofluorobenzene (DNFB), an inhibitor of CKs, shifted Egly in the depolarizing direction. In primary cortical neurons expressing CKB, the GABA reversal potential was also shifted in the depolarizing direction by DNFB. Our findings suggest that, in the cellular micro-environment, CKB activates the KCC2 function.

Animals↗

PubMed2005

Reducing the migration of di-2-ethylhexyl phthalate from polyvinyl chloride medical devices.

We attempted to determine the processing conditions for decreasing the migration of phthalate esters, particularly di-2-ethylhexyl phthalate (DEHP), from polyvinyl chloride (PVC) products using a drug solvent after dilution based on the package insert. PVC sheets and PVC tubing were subjected to optical irradiation (ultraviolet (UV), visible light irradiation) and heat treatment to determine whether they are deteriorated by these treatments. UV irradiation to one side of the PVC sheet decreased the levels of DEHP migration from the sheets by almost 50%, although the amount of DEHP content in PVC sheet was observed no significant change. On the other hand, the levels of DEHP migrating from the inner surface of PVC tubing UV-irradiated from the outer surface were not decreased compared with the control. Therefore, the surface structure was examined by conducting Fourier transform infrared spectroscopy (FT-IR), electron spectroscopy for chemical analysis (ESCA) and static angle of contact measurement. In FT-IR analysis, we found that the UV-irradiated PVC sheets were exhibited broadened absorption bands with time. In ESCA analysis, the chlorine content was decreased and the oxygen content was increased with time in UV-irradiated PVC sheets. Moreover, the other treated PVC sheets shows no significant change compared with the non-UV-irradiated PVC sheet. Therefore, the surface structure of the UV-irradiated PVC sheet was changed. As a result, the migration of DEHP from PVC products can be decreased with simple treatment, such as UV-irradiation. This could be a useful method to develop novel PVC products.

Cyclosporine↗

PubMed2005

Usefulness of a new grading system based on coronary flow velocity pattern in predicting outcome in patients with acute myocardial infarction having percutaneous coronary intervention.

In acute myocardial infarction, the coronary blood flow velocity waveform changes with the damage in the infarcted myocardium. We developed a grading system using the shorter diastolic deceleration time (DDT), appearance of systolic flow reversal (SFR), and disappearance of systolic anterograde flow. We studied 72 patients with a first anterior acute myocardial infarction. Doppler guidewire monitoring and myocardial contrast echocardiography were performed 10 and 15 minutes after percutaneous coronary intervention, and left ventriculography was performed at discharge (24 +/- 2 days) to measure regional wall motion (SD/chord). Patients were classified into 4 groups according to the coronary blood flow velocity pattern: group I (n = 39), DDT >or=600 ms; group II (n = 10), DDT <600 ms; group III (n = 17), DDT <600 ms with SFR; and group IV (n = 14), DDT <600 ms with SFR and without systolic anterograde flow. The no-reflow phenomenon was observed in no patients in group I, in 3 in group II, in 11 in group III, and all 14 patients in group IV. Regional wall motion was highest in group I and decreased with increasing group number (groups I, II, III, and IV, -1.45 +/- 0.80, -2.36 +/- 0.60, -2.90 +/- 0.50, and -3.20 +/- 0.52 SD/chord, respectively). With the progression of damage in the infarcted myocardium, the DDT shortened first, followed by the appearance of SFR, and then the disappearance of systolic anterograde flow. In conclusion, analysis of the coronary blood flow velocity pattern allows assessment of the severity of microvascular dysfunction and prediction of left ventricular functional outcomes.

Aged↗

PubMed2005

Development of a simple method for predicting the levels of di(2-ethylhexyl) phthalate migrated from PVC medical devices into pharmaceutical solutions.

This study deals with the development of a simple method for predicting the elution levels of di-2-ethylhexyl phthalate (DEHP) from medical devices made of polyvinyl chloride (PVC) by using the physicochemical properties of pharmaceutical injections as a marker. GC-MS analysis showed that the release of DEHP from medical grade PVC product was concentration-dependently increased by extraction with two kinds of lipophilic injections (Sandimmun and Prograf) and three kinds of surfactants (HCO-60, Tween 80, and SDS). The solubility of lipophilic pigments such as Sudan III, methyl yellow, and 1,4-diamino-anthraquinone against these solutions were also increased in a concentration-dependent manner, in which methyl yellow showed the highest response regarding the increase of optical density (O.D.). Further, electrical conductivity and static contact angle to the PVC sheet of the solutions were also increased or decreased in the same manner. As a result of the comparative study, significant correlation was found between DEHP release levels and these three physicochemical properties, particularly methyl yellow solubility, of the solutions tested. To evaluate the relationship in detail, DEHP release levels from PVC tubing and methyl yellow solubility of 53 injections used in gynecologic and obstetric fields were determined. None of the hydrophilic medicines showed any significant release of DEHP, and all showed low solubility of methyl yellow. On the other hand, the lipophilic medicines releasing a large amount of DEHP showed high solubility of methyl yellow (greater than O.D. 0.8). These results indicate that a significant proportional relationship exists between DEHP release potency and methyl yellow solubility of pharmaceutical solutions, and the risk of DEHP exposure to the patients administered pharmaceuticals through transfusion set could be easily predicted by the solubility test without complicated elution tests of DEHP using GC-MS or LC-MS.

Diethylhexyl Phthalate↗

PubMed2005

Systematic analysis and overall toxicity evaluation of dioxins and hexachlorobenzene in human milk.

A systematic method for analyzing dioxins (PCDDs, PCDFs and dioxin-like PCBs), hexachlorobenzene (HCB), heptachlor epoxide and beta-hexachlorocyclohexane (HCH) in human milk was developed to determine the residual amount of HCB in human milk and to evaluate the overall toxicity of both dioxins and HCB in human milk. The fractionation behavior of HCB on chromatography with silica gel, alumina, and activated carbon/silica gel, and the concentrated sulfuric acid decomposition method, which is widely used as a dioxin cleanup method, were studied in order to make the preprocessing operation for HCB measurement compatible with that for conventional dioxin measurement. HCB was found to be eluted in the 2% dichloromethane (DCM)/hexane 60 ml fraction from an alumina column. Heptachlor epoxide and a part of beta-HCH were eluted in the 10% DCM/hexane 50 ml fraction from a silica gel column, while the remaining beta-HCH was eluted in the 25% DCM/hexane 60 ml fraction from an activated carbon/silica gel column. Moreover, HCB showed significant correlation with dioxin congeners having high toxicity equivalence factors (TEFs). The results suggest that the exposure route to HCB and its accumulation behavior in the human body are similar to those of the dioxins.

Chemistry Techniques, Analytical↗